Non-coding RNAs are involved in tumor cell death and affect tumorigenesis, progression, and treatment: a systematic review

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.

editing, and protein translation (Bahreini et al., 2021).An increasing number of studies have demonstrated that non-coding RNAs regulate tumor cell death by acting directly on cell death-related proteins or acting indirectly on downstream targets or pathways.In recent years, tremendous progress has been made in the study of the molecular mechanisms underlying the regulation of tumor cell death by non-coding RNAs, which is of great significance for elucidating the mechanisms of tumorigenesis and tumor development and guiding the treatment and intervention of tumors based on cell death.This article reviews the progress of research from this aspect.

Classification and regulatory mechanisms of cell death
At present, the common types of regulatory cell death are autophagy, ferroptosis, and pyroptosis (Buchser et al., 2012;Green, 2019).The differences in these processes are shown in Supplementary Table S1 (Additional File S1).Autophagy is a highly conserved self-digestion process in eukaryotic cells that extensively regulates cell growth, development, senescence, and death.In some cases, autophagy acts on cell death as autophagic cell death.Autophagy is the process by which cells use lysosomes to degrade damaged organelles and macromolecular substances to maintain homeostasis.The cells first form a monolayer or bilayer membrane that develops into a vesicle-like autophagosome, which then fuses with a lysosome to form an autolysosome, leading to the lysosomal hydrolase degradation of the contents and the recycling of the products (New and Tooze, 2019;Chen et al., 2022), as shown in Supplementary Figure S1 (Additional File S2).
Ferroptosis is a newly identified form of regulatory cell death caused by the abnormal accumulation of lipid reactive oxygen species (ROS).Ferroptosis and iron metabolism, glutathione metabolism, and lipid peroxidation are closely related, Thus, a large number of molecules have roles in ferroptosis, including transferrin receptor 1, ferritin, cystine/glutamate reverse transporter, glutathione peroxidase 4 (GPX4), and lipoxygenase (Rochette et al., 2022).The regulatory mechanisms of ferroptosis are described in Supplementary Figure S2 (Additional File S3).
Pyroptosis is a novel form of programmed cell death that depends mainly on the cleavage and activation of gasdermin protein by the inflammasome-activating caspase family of proteins, which then translocates to the membrane to form holes, leading to cell swelling, cytosolic outflow, and cell membrane rupture (Zhang et al. 2021c).The regulatory mechanism of pyroptosis is shown in Supplementary Figure S3 (Additional File S4).

Features and functions of noncoding RNAs
Non-coding RNAs are transcribed, but are not translated into a protein, and include mainly miRNAs, lncRNAs, and circRNAs (Bahreini et al., 2021).The features and functions of miRNAs, lncRNAs, and circRNAs are summarized in Supplementary Table S2 (Additional File S1).miRNAs are an endogenous class of RNA molecules that are 21-25 nucleotides in length.miRNAs regulate various metabolic pathways at the transcription and translation levels and have key roles in regulating tumor cell growth, migration, invasion, and chemoresistance (Ambros, 2001).lncRNAs are RNA molecules greater than 200 nucleotides in length, with or without an open reading frame, that are involved in transcriptional silencing and activation, chromosome modification, and nuclear transport (Anastasiadou et al., 2018).circRNAs are non-coding RNA molecules formed by reverse splicing that are stable and not easy to degrade.circRNAs are derived from introns or exons, can act as RNA sponges, and can also be combined with proteins, so as to participate in the regulation of gene expression and affect protein function (Zheng et al., 2017).

Role of miRNAs in tumor cell death for tumorigenesis, development, and treatment miRNAs and autophagy
In recent years, miRNAs have been shown to be involved mainly in influencing the role of autophagy in lung cancer, multiple myeloma, kidney cancer, oral cancer, liver cancer, nasopharyngeal carcinoma (NPC), melanoma, thyroid cancer, and prostate cancer (PCa), as summarized in Table 1.For example, miRNA-153-3p expression is low in gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, and its expression level is negatively correlated with that of the autophagic activity marker tubulin 1 light chain 3. miRNA-153-3p overexpression inhibits the occurrence of autophagy and enhances sensitivity to gefitinib by downregulating the expression of autophagy-related 5 homolog (ATG5) (Zhang et al., 2019a).The expression levels of miRNA-125b and miRNA-143 are significantly correlated with the concentrations of beta-2-microglobulin, albumin, and hemoglobin.
The upregulation of miRNA-125b and downregulation of miRNA-143 both promote autophagy, thus inhibiting apoptosis in myeloma cells (Shang et al., 2018).miR-30a inhibits autophagy in renal cancer cells by downregulating the expression of Beclin-1 and interferes with sorafenib-mediated cell apoptosis through an autophagy-dependent pathway (Zheng et al., 2015).Isoliquiritigenin promotes apoptosis and autophagy in oral squamous cell carcinoma (OSCC) cells by downregulating the expression of miRNA-21 and miRNA-155, which provides new targets for the treatment of OSCC (Mohamed et al., 2022).Mitogeninducible gene 6 (Mig-6) promotes apoptosis and autophagy in hepatocellular carcinoma (HCC) cells by regulating the expression of miR-193a-3p (Qu et al., 2022).miR-1278 specifically regulates the expression of ATG2B to promote autophagy in NPC cells, thereby increasing the chemical resistance of NPC cells to cisplatin; miR-1278 may become a novel therapeutic target for the treatment of NPC (Zhao et al., 2020).miR-30a-5p inhibits ATG5-mediated autophagy in lung SCC cells and slows the progression of lung SCC through the autophagy pathway (Yang et al., 2021b).miR-18a-5p expression is significantly increased in melanoma tissues and cell lines, and the expression of ephrin type-A receptor 7 (EPHA7) is negatively regulated to promote the proliferation of melanoma cells and inhibits apoptosis and autophagy, which provide clues to reveal the pathogenesis of miRNA-mediated melanoma (Guo Y. et al., 2021).miR-216a expression is downregulated in colorectal cancer (CRC) tissues, and autophagy is inhibited by the transforming growth factor beta 1 (TGF-β)/microtubule-associated protein 1S (MAP1S) pathway (Wang Y. et al., 2019).The high expression of miR-221/222 is associated with the regional lymph node and distant metastasis stage of papillary thyroid carcinoma, and miR-221/ 222 target ATG10 expression, thus inhibiting autophagy and apoptosis in papillary thyroid carcinoma cells (Shen et al., 2020).In PCa cells, the upregulation of miR-381 expression suppresses the expression of recombinant reelin and then suppresses the activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway to promote apoptosis and autophagy (Liao and Zhang, 2020).

miRNAs and pyroptosis
Studies of the roles of miRNAs in pyroptosis for the development of osteosarcoma, neurocytoma, glioma, cervical cancer, and breast cancer are summarized in Table 3.For example, the downregulation of miR-181a expression in osteosarcoma cells activates the expression of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) to promote pyroptosis and inhibit tumor growth (Tian et al., 2020).miR-195 expression is significantly downregulated in neuroblastoma SH-SY5Y cells infected with enterovirus A71, and miR-195 binds to NLR family member X1 and NLRs to regulate the pyroptosis induced by enterovirus A71 infection (Zhu X. et al., 2021).In glioma tissues as well as the glioblastoma cell lines U87 and T98G, caspase-1 expression is increased while miR-214 expression is significantly downregulated, and miR-214 regulates caspase 1-mediated pyroptosis to inhibit cell proliferation and migration, providing a novel intervention for glioma (Jiang et al., 2017).miR-214 expression is significantly downregulated in cervical cancer cell lines and regulates NLRP3 expression, which induces pyroptosis (Yu et al., 2020).miRNA-155-5p expression is upregulated in triple-negative breast cancer cells, while downregulation of its expression induces pyroptosis and enhances the role of cetuximab in the MDA-MB-468 xenograft model (Xu W. et al., 2021).

lncRNAs and ferroptosis
Studies examining the involvement of lncRNAs in ferroptosis for the occurrence, development, and metallurgical treatment of HCC, gastric cancer, colon cancer, PCa, kidney cancer, and lung cancer are summarized in Table 5.For example, the high expression of brainderived neurotrophic factor antisense RNA (BDNF-AS) is positively correlated with the progression and poor prognosis of gastric cancer (Huang G. et al., 2022).BDNF-AS overexpression protects gastric cancer cells from ferroptosis and promotes the progression of gastric cancer.The BDNF-AS/WD repeat domain 5 (WDR5)/F-box and WD repeat domain-containing 7 (FBXW7) axis regulates ferroptosis in gastric cancer cells by affecting the ubiquitination of voltagedependent anion channel 3 (VDAC3) (Huang G. et al., 2022).CBS mRNA stabilizing lncRNA (CBSLR) interacts with YTH domain linker protein 2 (YTHDF2) to form the CBSLR/YTHDF2/cystathionine betasynthase (CBS) signal axis, which reduces the stability of CBS mRNA by enhancing the binding of YTHDF2 to the m 6 A-modified coding sequence of CBS mRNA.This protects gastric cancer cells from iron death and leads to resistance to chemotherapy drugs (Yang H. et al., 2022).LINC01606 protects colon cancer cells from ferroptosis by reducing the concentration of iron, lipid ROS, and mitochondrial superoxide, and by increasing mitochondrial membrane potential, while LINC01606 and Wnt/β-catenin form a positive feedback regulatory loop that further inhibits ferroptosis (Luo et al., 2022).lncPVT1 depletion accelerates ferroptosis in HCC cells, and decreased miR-214-3p expression and increased GPX4 expression reverse this effect and promote 4-ketamine-induced ferroptosis (He et al., 2021).In HCC cells, overexpression of nuclear paraspeckle assembly transcript 1 (NEAT1) enhances ferroptosis and the antitumor of erastin and RSL3; NEAT1 plays a role in ferroptosis by regulating the expression of miR-362-3p and myoinositol oxygenase (MIOX) (Zhang Y. et al., 2022).Prostate cancerassociated transcript 1 (PCAT1) suppresses ferroptosis and enhances docetaxel resistance in PCa cells; PCAT1 inhibits the expression of miR-25-3p, thus promoting SLC7A11 expression, while transcription factor AP-2 γ activates PCAT1 expression, and finally reduces ferroptosis and enhances resistance to chemotherapeutic agents (Jiang X. et al., 2022).SLC16A1-antisense nucleic acid 1 (AS1) is highly expressed in kidney cancer, and is associated with overall survival; knockdown of SLC16A1-AS1 expression suppresses the proliferation and migration of kidney cancer cells, and SLC16A1-AS1 induces ferroptosis in kidney cancer through the miR-143-3p/SLC7A11 axis (Li et al., 2022).The metallothionein 1D pseudogene (MT1DP) downregulates miR-365a-3p expression by stabilizing the expression of nuclear factor-erythroid 2 p45-related factor 2, and further promotes ferroptosis in lung cancer cells (Gai et al., 2020).Overexpression of lncRNA H19 eliminates the anticancer effects of curcumin in lung cancer cells, whereas knockdown of H19 expression promotes curcumin-induced ferroptosis; lncRNA H19 acts as a competing endogenous RNA for miR-19b-3p, thereby enhancing the transcriptional activity of its endogenous target, ferritin heavy chain 1 (FTH1) (Zhang R. et al., 2022).

lncRNAs and pyroptosis
At present, research on the participation of lncRNAs in pyroptosis in tumors focuses mainly on using bioinformatics technology to predict the role of lncRNAs associated with pyroptosis in tumor diagnosis, treatment, and prognosis.However, molecular biology experiments are needed to verify their potential functions.For example, investigators downloaded the sequencing results from a total of 454 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database and identified 19 prognostic lncRNAs related to pyroptosis (Huang H. et al., 2022).Based on RNA sequencing data from the TCGA database, researchers analyzed 14 lncRNAs associated with pyroptosis that may be prognostic markers and promising therapeutic targets in head and neck SCC (Zhu W. et al., 2021).Pyroptosis-associated lncRNAs are associated with the tumor immune microenvironment, which may provide a new indicator for the selection of patients with ovarian cancer for immunotherapy (Zhang et al., 2021e).
According to analyses of the TCGA and China Glioma Genome Atlas databases, a pyroptosis-related lncRNA model was established by using consensus clustering and weighted gene co-expression network analysis, and glioblastoma patients with a high pyroptosis-related lncRNA score were found to have a richer immune infiltrate, higher immune checkpoint gene expression, and better response to immunotherapy, but worse response to chemotherapy (Xing et al., 2022).In gastric adenocarcinoma, HAND2-AS1, LINC01354, RP11-276H19.1, and PGM5-AS1 were suggested to be involved in pyroptosis, which could be used to guide effective patient prognosis and to provide evidence for the development of molecular-targeted therapies associated with pyroptosis (Wang Z. et al., 2022).lncRNA-XIST knockdown triggers pyroptosis mediated by the miR-335/superoxide dismutase 2/ROS signaling pathway, thereby inhibiting the progression of NSCLC (Liu et al., 2019).An lncRNA profile including ELFN1-AS1, PCAT6, TNRC6C-AS1, and ZEB1-AS1 related to pyroptosis could accurately predict the prognosis of CRC patients (Chen S. et al., 2021).
An investigator-constructed risk model containing 10 lncRNAs associated with pyroptosis that were identified as independent predictors of overall survival in breast cancer patients, with RP11-459E5.1, RP11-1070N10.3,and RP11-817J15.3downregulation, was significantly associated with worse overall survival (Yang et al., 2021d).Eight pyroptosis-associated lncRNAs were identified by using a coexpression network of genes and lncRNAs and by further screening with univariate Cox regression analysis, which may be potential molecular markers and therapeutic targets in patients with bladder cancer (Lia et al., 2022).A novel risk score for pyroptosis-related lncRNAs could be used as a promising prognostic biomarker for HCC patients and may help to guide precision drugs and immunotherapy (Wang T. et al., 2022).Based on transcriptomic data, miRNA sequencing data, and related clinical information downloaded from the TCGA database, and constructed a competing endogenous RNA regulatory network that included 132 lncRNAs and 7 miRNAs, and established 11 lncRNA risk models related to pyroptosis, which has good prognostic value and can predict the immunotherapy outcome of colon adenocarcinoma (Tan et al., 2022).

Role of circRNAs in tumor cell death for tumorigenesis, development, and treatment circRNAs and autophagy
CircRNAs are involved mainly in the influence of autophagy on the occurrence, development, and treatment of breast cancer, SCC, NSCLC, bladder cancer, gastric cancer, AML, cervical carcinoma, osteosarcoma, Bozzolo's disease, PCa, epithelial ovarian cancer, and pancreatic ductal adenocarcinoma, as summarized in Table 6.For example, circDNMT1 increases the proliferation of breast cancer cells by promoting cell autophagy (Du et al., 2018).Ectopically expressed circDNMT1 promotes the nuclear translocation of p53 and AU-rich element RNA-binding factor 1 (AUF1); the nuclear translocation of p53 induces autophagy, while the nuclear translocation of AUF1 reduces the instability of Dnmt1, ultimately increasing DNMT1 translation (Du et al., 2018).While ciRS-7 is highly expressed in triple-negative breast cancer, it suppresses rapamycin-induced autophagy in esophageal SCC, and miR-1299 promotes rapamycininduced autophagy in esophageal SCC; ciRS-7 interacts with miR-1299 and regulates epidermal growth factor receptor (EGFR) expression to inhibit autophagy in esophageal SCC cells (Meng et al., 2020).circCUL2 overexpression inhibits the proliferation and autophagy of CRC cells and inhibits CRC progression through the miR-208a-3p/ PPP6C signaling pathway (Yang B. L. et al., 2022).circUBAP2 induces autophagy in CRC cells in vitro and in vivo; circUBAP2 interacts directly with miR-582-5p and regulates the expression of forkhead box protein O1 (FOXO1) to promote CRC progression and metastasis (Chen F. et al., 2021).Silencing of circHIPK3 expression significantly inhibits the proliferation of lung cancer cells and induces autophagy; circHIPK3 has potential clinical value in evaluating the prognosis of lung cancer (Chen et al., 2020).High hsa_circ_0085131 expression is associated with the recurrence of NSCLC; hsa_circ_0085131 interacts with miR-654-5p to promote the expression of ATG7, thus enhancing the resistance of NSCLC cells to cisplatin (Kong, 2020).Reduced hsa_ circ_0007813 expression inhibits the proliferation, migration, and autophagy of bladder cancer cells in vitro and in vivo; hsa_circ_ 0007813 binds to hsa-miR-361-3p and regulates the expression of insulin-like growth factor 2 receptor, thereby affecting bladder cancer progression (Zhang et al., 2021d).Silencing of circ_ 0001658 expression reduces the viability and autophagy of gastric cancer cells, and circ_0001658 acts by binding miR-182 and inhibiting the expression of member RAS oncogene family (RAB10) (Duan et al., 2022).circRNA-poly (A)-nuclease deadenylation complex subunit 3 (circPAN3) increases the drug resistance of AML cells by regulating autophagy, and the AMPK/mTOR signaling pathway plays a key role in this process (Shang et al., 2019).Knockdown of circRNA TOPBP1-interacting checkpoint and replication regulator (circTICRR) expression activates autophagy in cervical cancer cells; circTICRR binds to F287/F289 in the ribonucleotide reductase regulatory subunit M3 domain of human antigen R (HuR) and increases the expression of glutamate dehydrogenase 1 (GLUD1) protein, ultimately promoting autophagy (Zhu et al., 2022).circMRPS35 increases microtubule associated protein 1 light chain 3 (LC3) and Beclin-1 expression to promote autophagy in osteosarcoma cells (Jiang C. et al., 2022).After downregulation in osteosarcoma cells, circCRIM1 inhibits cell proliferation, promotes cell autophagy, and acts on the miR-432-5p/HDAC4 axis to inhibit osteosarcoma growth (Liu J. et al., 2020).The hsa_circ_0003489/miR-874-3p/HDAC1 axis balances apoptosis and autophagy in multiple myeloma cells, silences the expression of hsa_circ_0003489, inhibits autophagy, and enhances the sensitivity of multiple myeloma cells to bortezomib (Tian et al., 2021).

circRNAs and ferroptosis
The influence of circRNAs on ferroptosis in the occurrence, development, and treatment of HCC, lung cancer, cervical cancer, thyroid carcinoma, OSCC, breast cancer, glioma, thyroid papillary carcinoma, rectal carcinoma, and acute lymphoblastic leukemia (ALL) is summarized in Table 7.For example, knockdown of circ0097009 expression inhibits the proliferation and invasion of HCC cells; circ0097009, as a competing endogenous RNA, adsorbs miR-1261 and regulates the expression of SLC7A11, a key regulator of ferroptosis, to affect the occurrence and development of liver cancer (Lyu et al., 2021).The expression of cIARS (hsa_circ_ 0008367) is significantly upregulated in HCC cells after treatment with sorafenib.Downregulation of cIARS expression inhibits ferroptosis, and cIARS inhibits AlkB homolog 5, RNA demethylase (ALKBH5)-mediated autophagy and inhibits sorafenib-induced ferroptosis (Liu Z. et al., 2020).circFOXP1 expression is significantly upregulated in lung cancer tissues, and knockdown of circFOXP1 expression inhibits the viability of lung cancer cells and promotes lung cancer progression by inhibiting ferroptosis (Li and Liu, 2022).circRNA denticleless E3 ubiquitin protein ligase homolog (circDTL) expression is upregulated in NSCLC cells, and knockdown of its expression promotes apoptosis and ferroptosis in NSCLC cells; circDTL functions through the miR-1287-5p/GPX4 axis, which provides a potential target for NSCLC treatment (Shanshan et al., 2021).circLMO1 overexpression in vitro and in vivo suppresses the growth and metastasis of cervical cancer, and circLMO1 inhibits cervical cancer progression through ferroptosis mediated by the miR-4291/ACSL4 axis (Ou et al., 2022).Knockdown of circ_ 0067934 expression in vitro and in vivo induces the proliferation and apoptosis of thyroid cancer cells; circ_0067934 inhibits ferroptosis in thyroid cancer cells through the miR-545-3p/ SLC7A11 axis (Wang et al., 2021).Reduced circFNDC3B expression inhibits the growth and ferroptosis of OSCC cells, and the circFNDC3B/miR-520d-5p/SLC7A11 axis promotes the progression of OSCC (Yang et al., 2021a).circRHOT1 acts via the miR-106a-5p/signal transducer and activator of transcription 3 (STAT3) axis to promote the malignant progression of breast cancer and alleviates ferroptosis, providing new insights into the molecular mechanisms underlying the development of breast cancer (Zhang et al., 2021a).In glioma tissues and cells, the expression of the circRNA tau tubulin kinase 2 (circTTBK2) and integrin subunit beta 8 (ITGB8) is upregulated, and circTTBK2 targets ITGB8 expression to promote glioma cell proliferation, invasion, and ferroptosis (Zhang H. Y. et al., 2020).Knockdown of circRNA kinesin family member 4A (circKIF4A) expression inhibits the growth and migration of papillary thyroid cells; the circKIF4A-miR-1231-GPX4 axis plays an important role in promoting the proliferation and ferroptosis of papillary thyroid cancer cells (Chen W. et al., 2021).In rectal cancer tissues, the expression of circRNA ATP-binding box subfamily B member 10 (circABCB10) and C-C motif chemokine ligand 5 (CCL5) is upregulated, while miR-326 is knocked down to promote ferroptosis; the circABCB10/ miR-326/CCL5 axis affects rectal cancer cell ferroptosis (Xian et al., 2020).Knockdown of circ_0000745 expression in an ALL cell line suppresses cell cycle progression and glycolysis, and triggers apoptosis and ferroptosis; circ_0000745 binding to miR-494-3p induces neuroepithelial cell transforming 1 (NET1) expression and promotes the development of ALL (Yang X. et al., 2022).circPVT1 enhances the sensitivity of esophageal SCC cells to 5fluorouracil and regulates the Wnt/β-catenin pathway and ferroptosis via the miR-30a-5p/frizzled class receptor 3 (FZD3) axis (Yao et al., 2021).

circRNAs and pyroptosis
Pyroptosis is an important natural immune response of the body that plays a key role in fighting infection (Deng et al., 2022).circRNAs belong to a class of abundant non-coding RNAs, with stability and specificity, and thus have great potential in cancer treatment (Zhang et al., 2021b).The involvement of circRNAs in the role of pyroptosis in tumors has not been studied in depth.Investigators selected 1,875 differentially expressed circRNAs in unirradiated and irradiated lung cancer A549 cells (Zhang T. et al., 2022).Knockdown of circRNA Nei-like DNA glycosylase 3 (circNEIL3) expression was shown to promote radiation-induced pyroptosis.However, circNEIL3 overexpression had the opposite effect; by binding to miR-1184, circNEIL3 released the inhibitory effect of miR-1184 on PIF1 5′-to-3′ DNA helicase (PIF1) to induce DNA damage and trigger the activation of the absent in melanoma 2 inflammasome.The circNEIL3/miR-1184/PIF1 axis may be a new and promising clinical treatment strategy for lung cancer (Zhang T. et al., 2022).

Conclusion and future directions
Clinical and basic research into cancer, as a profound public health issue worldwide, has made many breakthroughs in recent years, but we still lack the ability to control tumor morbidity and mortality.How to kill tumor cells accurately and protect normal cells is the last and most important focus of tumor research.With our deepening understanding of intracellular molecules, an increasing number of molecules have been identified with roles in tumor progression, and the participation of non-coding RNAs in cell death plays a key role in tumor occurrence and development.However, under different biological backgrounds, regulated cell death may play very different biological roles.The functions of most cell death-related genes in tumors have not been studied thoroughly, and the signal of regulated cell death in tumors is also undecipherable.Therefore, revealing the regulatory mechanisms of non-coding RNAs involved in cell death in cancer, identifying potential therapeutic cell death targets of cancer, and developing novel immunotherapies based on the non-coding RNAs involved in cell death will have great and farreaching significance for conquering cancer.